'One of the biggest moments': The breakthrough that will change Mark's life

Eunice Lee, with her son, Mark Lee, who has successfully completed a gene therapy trial for haemophilia, and her granddaughters, Grace, 10, and Violet ,18 months, and her daughter in law, Shannon Salo, at the Charles Perkins Centre at RPA in Sydney. Eunice lost two other sons to haemophilia. 7th December 2017 Photo: Janie Barrett

A new gene therapy for haemophilia B has the potential to cure the life-threatening bleeding disorder in one dose, groundbreaking research suggests.

Researchers at the Royal Prince Alfred Hospital in Sydney have called their findings a major breakthrough for people with the hereditary disorder caused by defective or missing coagulation factors, which prevents their blood from clotting properly.

Haemophilia patients are dependent on multiple infusions of factor concentrates, as many as three a week, to guard against major bleeding that can be triggered by even minor injuries. People with haemophilia B - about 20 per cent of all cases - have a factor IX deficiency.

The team of Australian and US researchers found that by injecting these patients with a gene therapy called factor IX Padua (R338L), their bodies kept expressing the coagulant on their own.

All 10 men with haemophilia B in the trial responded overwhelmingly positively, the researchers reported.

Nine of the 10 patients had no bleeds, and eight out of 10 needed no further infusions over the one-year follow-up period.

After more than two decades of work, the researchers had discovered "what may be a permanent cure" for haemophilia, said co-author Professor John Rasko, haematologist and director of Cell and Molecular Therapies at RPA.

"We now know how to beat the immune response," Professor Rasko said.

"Hopefully, it creates a correction for the rest of the patient's life."

The rate of bleeding dropped dramatically from an average of 11.1 bleeds per year to 0.4 with not serious side-effects, according to the researchers led by haemotology experts at the Children's Hospital of Philadelphia, Pennsylvania.

"We are confident ... that this is life-changing for our patients and without a doubt, this is the best outcome to date for haemophilia gene therapy in the world," Professor Rasko said.

Mark Lee, one of the men who took part in the trial, had to undergo infusions up to three times a week since birth.

His two brothers died of complications from haemophilia B when they were children, just 11 weeks, and 16 years old. His two young daughters and niece are carriers for haemophilia.

He has not had a single bleed since his gene therapy infusion.

"Now I know that if they have affected children, it will be one injection and they can live normal lives," Mr Lee, 38, said.

He choked up as he described being able to stand up and walk off an aeroplane with the rest of the passengers after the treatment. His entire life he had had to wait until the cabin emptied before slowly standing in pain, burdened by micro-bleeds in his knee and ankle joints that pooled during the flights.

"It was one of the biggest moments ... probably really small for most people but a big thing for me," he said.

His mother Eunice Lee said the treatment was "a godsend".

"[M]any nights over the last 40 years I've rocked him to sleep on the couch when he had pain in the joints because of bleeds.

"Now, with three granddaughters and the possibility of the hereditary [risk] going through them, this is just an unbelievable relief," she said.

Haemophilia B accounts for roughly 20 per cent of all haemophilia cases. About 500 men in Australia have the B subtype.

An NEJM editorial called the trial results an important milestone for haemophilia B patients, advocates and their families, "who now are within touching distance of having an ideal cure for this terrible disease".

"It does work, but it's early days yet," Professor Rasko said.

Further research is needed to determine the long term efficacy and safety of the treatment in larger patient groups.

The research team will also trial a tailored gene therapy for haemophilia A, caused by a factor VIII deficiency. This subtype accounts for 80 per cent of all haemophilia and affects more than 2300 Australians.

The trial was funded by biotech company Spark Therapeutics and Pfizer.

Spark Therapeutics, attached to the Children's Hospital of Philadelphia, is funding the commercialisation of the therapy, which uses a viral vector to piggyback the transgene R338L into the liver.

The researchers hoped their work would also further efforts to use gene therapies to treat thousands of other genetic disorders, including blindness and and neurodegenerative diseases. Several clinical trials have recently reported successes using gene therapy to treat conditions including severe combined immunodeficiency, adrenoleukodystrophy and spinal muscular atrophy (SMA).

Director of the NSW Office of Health and Medical research Tony Penna said the breakthrough findings, which had the potential to save thousands of lives worldwide, was possible because of the dedication of the researchers and NSW's cutting-edge gene and cell therapy facilities.

"This is a world-first that all Australians can be proud of and highlights the need for both public and private investment in medical research," Dr Penna said.